Summary The popularity of electronic cigarettes (e-cigs) has grown at a startling rate since their introduction to the US market 10 years ago, with sales expected to outpace tobacco products within a decade. E-cigs are often per- ceived as a safer alternative to tobacco-based cigarettes, which is unsettling given the limited science on its chemistry and paucity of knowledge on long-term health effects of aerosol inhalation. Particularly alarming is marketing directed extensively toward adolescents, which indicates that young people are the key target mar- ket of e-cig companies. Further, there is no evidence among cigarette smokers that alternative e-cig use leads to smoking cessation. In fact, recent data suggests e-cig users who have never smoked conventional ciga- rettes are more likely to take up tobacco cigarette smoking within six months. E-cigs yield mainstream aerosols with particle concentrations similar or even higher than those in conventional cigarettes. Indeed, e-cig ?vapers? repeatedly inhale high concentrations of volatile organic compounds and, importantly, ultrafine particles and free radicals. The latter are then taken up by the alveoli where they translocate into the vascular space leading to endothelial dysfunction (EDF), the prime promoter of atherosclerotic cardiovascular disease. The current tools available for detecting the earliest presymptomatic vascular changes, brought about by EDF, are relatively limited. Building on recent work in the investigators' laboratory in which we quantified multiple functional and mechanical surrogate measures of EDF in tobacco cigarette smokers we propose to examine the effects of aerosol inhalation by quantitative MRI (qMRI) and compare the resulting biomarkers with pharmacologic measures. We hypothesize that the oxidative stress exerted by e-cig aerosol causes EDF comparable to that from cigarette smoke exposure and that MRI-derived biomarkers parallel inflammatory indi- ces measured in serum. We will examine both acute and longer-term effects by assessing microvascular reac- tivity via dynamic femoral oximetry, arterial hyperemia, femoral artery flow-mediated dilation, central pulse- wave velocity and neurovascular reactivity, all as part of a single integrated MRI protocol. The outcome of the proposed project will provide new insight into the acute and chronic effects of e-cig aerosol inhalation in terms of surrogate markers of EDF and aid toward establishment of future public health advisories, particularly in juvenile e-cig consumers.